Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial

Lajos Pusztai; Christina Yau; Denise M. Wolf; Hyo S. Han; Lili Du; Anne M. Wallace; Erica String-Reasor; Judy C. Boughey; A. Jo Chien; Anthony D. Elias; Heather Beckwith; Rita Nanda; Kathy S. Albain; Amy S. Clark; Kathleen Kemmer; Kevin Kalinsky; Claudine Isaacs; Alexandra Thomas; Rebecca Shatsky; Theresa L. Helsten; Andres Forero-Torres; Minetta C. Liu; Lamorna Brown-Swigart; Emmanuel F. Petricoin; Julia D. Wulfkuhle; Smita M. Asare; Amy Wilson; Ruby Singhrao; Laura Sit; Gillian L. Hirst; Scott Berry; Ashish Sanil; Adam L. Asare; Jeffrey B. Matthews; Jane Perlmutter; Michelle Melisko; Hope S. Rugo; Richard B. Schwab; W. Fraser Symmans; Doug Yee; Laura J. van't Veer; Nola M. Hylton; Angela M. DeMichele; Donald A. Berry; Laura J. Esserman

doi:10.1016/j.ccell.2021.05.009

Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial

Lajos Pusztai, Christina Yau, Denise M. Wolf, Hyo S. Han, Lili Du, Anne M. Wallace, Erica String-Reasor, Judy C. Boughey, A. Jo Chien, Anthony D. Elias, Heather Beckwith, Rita Nanda, Kathy S. Albain, Amy S. Clark, Kathleen Kemmer, Kevin Kalinsky, Claudine Isaacs, Alexandra Thomas, Rebecca Shatsky, Theresa L. HelstenAndres Forero-Torres, Minetta C. Liu, Lamorna Brown-Swigart, Emmanuel F. Petricoin, Julia D. Wulfkuhle, Smita M. Asare, Amy Wilson, Ruby Singhrao, Laura Sit, Gillian L. Hirst, Scott Berry, Ashish Sanil, Adam L. Asare, Jeffrey B. Matthews, Jane Perlmutter, Michelle Melisko, Hope S. Rugo, Richard B. Schwab, W. Fraser Symmans, Doug Yee, Laura J. van't Veer, Nola M. Hylton, Angela M. DeMichele, Donald A. Berry, Laura J. Esserman

Research output: Contribution to journal › Article › peer-review

Abstract

The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%–37%), hormone receptor (HR)-positive/HER2-negative (14%–28%), and triple-negative breast cancer (TNBC) (27%–47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP (pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR 9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.

Original language	English (US)
Pages (from-to)	989-998.e5
Journal	Cancer cell
Volume	39
Issue number	7
DOIs	https://doi.org/10.1016/j.ccell.2021.05.009
State	Published - Jul 12 2021

Keywords

DNA repair inhibitor
breast cancer
clinical trial
immunotherapy

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2021.05.009

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Pusztai, L., Yau, C., Wolf, D. M., Han, H. S., Du, L., Wallace, A. M., String-Reasor, E., Boughey, J. C., Chien, A. J., Elias, A. D., Beckwith, H., Nanda, R., Albain, K. S., Clark, A. S., Kemmer, K., Kalinsky, K., Isaacs, C., Thomas, A., Shatsky, R., ... Esserman, L. J. (2021). Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Cancer cell, 39(7), 989-998.e5. https://doi.org/10.1016/j.ccell.2021.05.009

Pusztai, L, Yau, C, Wolf, DM, Han, HS, Du, L, Wallace, AM, String-Reasor, E, Boughey, JC, Chien, AJ, Elias, AD, Beckwith, H, Nanda, R, Albain, KS, Clark, AS, Kemmer, K, Kalinsky, K, Isaacs, C, Thomas, A, Shatsky, R, Helsten, TL, Forero-Torres, A, Liu, MC, Brown-Swigart, L, Petricoin, EF, Wulfkuhle, JD, Asare, SM, Wilson, A, Singhrao, R, Sit, L, Hirst, GL, Berry, S, Sanil, A, Asare, AL, Matthews, JB, Perlmutter, J, Melisko, M, Rugo, HS, Schwab, RB, Symmans, WF, Yee, D, van't Veer, LJ, Hylton, NM, DeMichele, AM, Berry, DA & Esserman, LJ 2021, 'Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial', Cancer cell, vol. 39, no. 7, pp. 989-998.e5. https://doi.org/10.1016/j.ccell.2021.05.009

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title = "Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial",

abstract = "The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%–37%), hormone receptor (HR)-positive/HER2-negative (14%–28%), and triple-negative breast cancer (TNBC) (27%–47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP (pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR 9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.",

keywords = "DNA repair inhibitor, breast cancer, clinical trial, immunotherapy",

author = "Lajos Pusztai and Christina Yau and Wolf, {Denise M.} and Han, {Hyo S.} and Lili Du and Wallace, {Anne M.} and Erica String-Reasor and Boughey, {Judy C.} and Chien, {A. Jo} and Elias, {Anthony D.} and Heather Beckwith and Rita Nanda and Albain, {Kathy S.} and Clark, {Amy S.} and Kathleen Kemmer and Kevin Kalinsky and Claudine Isaacs and Alexandra Thomas and Rebecca Shatsky and Helsten, {Theresa L.} and Andres Forero-Torres and Liu, {Minetta C.} and Lamorna Brown-Swigart and Petricoin, {Emmanuel F.} and Wulfkuhle, {Julia D.} and Asare, {Smita M.} and Amy Wilson and Ruby Singhrao and Laura Sit and Hirst, {Gillian L.} and Scott Berry and Ashish Sanil and Asare, {Adam L.} and Matthews, {Jeffrey B.} and Jane Perlmutter and Michelle Melisko and Rugo, {Hope S.} and Schwab, {Richard B.} and Symmans, {W. Fraser} and Doug Yee and {van't Veer}, {Laura J.} and Hylton, {Nola M.} and DeMichele, {Angela M.} and Berry, {Donald A.} and Esserman, {Laura J.}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = jul,

day = "12",

doi = "10.1016/j.ccell.2021.05.009",

language = "English (US)",

volume = "39",

pages = "989--998.e5",

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T1 - Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer

T2 - Results from the adaptively randomized I-SPY2 trial

AU - Pusztai, Lajos

AU - Yau, Christina

AU - Wolf, Denise M.

AU - Han, Hyo S.

AU - Du, Lili

AU - Wallace, Anne M.

AU - String-Reasor, Erica

AU - Boughey, Judy C.

AU - Chien, A. Jo

AU - Elias, Anthony D.

AU - Beckwith, Heather

AU - Nanda, Rita

AU - Albain, Kathy S.

AU - Clark, Amy S.

AU - Kemmer, Kathleen

AU - Kalinsky, Kevin

AU - Isaacs, Claudine

AU - Thomas, Alexandra

AU - Shatsky, Rebecca

AU - Helsten, Theresa L.

AU - Forero-Torres, Andres

AU - Liu, Minetta C.

AU - Brown-Swigart, Lamorna

AU - Petricoin, Emmanuel F.

AU - Wulfkuhle, Julia D.

AU - Asare, Smita M.

AU - Wilson, Amy

AU - Singhrao, Ruby

AU - Sit, Laura

AU - Hirst, Gillian L.

AU - Berry, Scott

AU - Sanil, Ashish

AU - Asare, Adam L.

AU - Matthews, Jeffrey B.

AU - Perlmutter, Jane

AU - Melisko, Michelle

AU - Rugo, Hope S.

AU - Schwab, Richard B.

AU - Symmans, W. Fraser

AU - Yee, Doug

AU - van't Veer, Laura J.

AU - Hylton, Nola M.

AU - DeMichele, Angela M.

AU - Berry, Donald A.

AU - Esserman, Laura J.

PY - 2021/7/12

Y1 - 2021/7/12

N2 - The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%–37%), hormone receptor (HR)-positive/HER2-negative (14%–28%), and triple-negative breast cancer (TNBC) (27%–47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP (pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR 9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.

AB - The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%–37%), hormone receptor (HR)-positive/HER2-negative (14%–28%), and triple-negative breast cancer (TNBC) (27%–47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP (pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR 9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.

KW - DNA repair inhibitor

KW - breast cancer

KW - clinical trial

KW - immunotherapy

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AN - SCOPUS:85109444638

SN - 1535-6108

VL - 39

SP - 989-998.e5

JO - Cancer cell

JF - Cancer cell

IS - 7

ER -

Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial

Abstract

Keywords

ASJC Scopus subject areas

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